PMID- 9819364
OWN - NLM
STAT- MEDLINE
DCOM- 19981231
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 102
IP  - 10
DP  - 1998 Nov 15
TI  - Reduced transplant arteriosclerosis in plasminogen-deficient mice.
PG  - 1788-97
AB  - Recent gene targeting studies indicate that the plasminogen system is implicated 
      in cell migration and matrix degradation during arterial neointima formation and 
      atherosclerotic aneurysm formation. This study examined whether plasmin 
      proteolysis is involved in accelerated posttransplant arteriosclerosis (graft 
      arterial disease). Donor carotid arteries from wild-type B10.A2R mice were 
      transplanted into either plasminogen wild-type (Plg+/+) or homozygous 
      plasminogen-deficient (Plg-/-) recipient mice with a genetic background of 75% 
      C57BL/6 and 25% 129. Within 15 d after allograft transplantation, leukocytes and 
      macrophages infiltrated the graft intima in Plg+/+ and Plg-/- recipient mice to a 
      similar extent. In Plg+/+ recipients, the elastic laminae in the transplant media 
      exhibited breaks through which macrophages infiltrated before smooth muscle cell 
      proliferation, whereas in Plg-/- recipients, macrophages failed to infiltrate the 
      transplant media which remained structurally more intact. After 45 d of 
      transplantation, a multilayered smooth muscle cell-rich transplant neointima 
      developed in Plg+/+ hosts, in contrast to Plg-/- recipients, in which the 
      transplants contained a smaller intima, predominantly consisting of leukocytes, 
      macrophages, and thrombus. Media necrosis, fragmentation of the elastic laminae, 
      and adventitial remodeling were more pronounced in Plg+/+ than in Plg-/- 
      recipient mice. Expression of the plasminogen activators (PA), urokinase-type PA 
      (u-PA) and tissue-type PA (t-PA), and expression of the matrix metalloproteinases 
      (MMPs), MMP-3, MMP-9, MMP-12, and MMP-13, were significantly increased within 15 
      d of transplantation when cells actively migrate. These data indicate that 
      plasmin proteolysis plays a major role in allograft arteriosclerosis by mediating 
      elastin degradation, macrophage infiltration, media remodeling, medial smooth 
      muscle cell migration, and formation of a neointima.
FAU - Moons, L
AU  - Moons L
AD  - Center for Transgene Technology and Gene Therapy, Flanders Interuniversity 
      Institute for Biotechnology, B-3000 Leuven, Belgium.
FAU - Shi, C
AU  - Shi C
FAU - Ploplis, V
AU  - Ploplis V
FAU - Plow, E
AU  - Plow E
FAU - Haber, E
AU  - Haber E
FAU - Collen, D
AU  - Collen D
FAU - Carmeliet, P
AU  - Carmeliet P
LA  - eng
GR  - HL-17964/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 9001-91-6 (Plasminogen)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - Arteriosclerosis/enzymology/genetics/*pathology
MH  - Carotid Arteries/enzymology/*pathology/transplantation
MH  - Cell Division
MH  - Cell Movement
MH  - Endothelium, Vascular/immunology/pathology
MH  - Host vs Graft Reaction
MH  - Immunohistochemistry
MH  - Macrophages/cytology
MH  - Male
MH  - Metalloendopeptidases/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/cytology
MH  - Plasminogen/genetics/*physiology
MH  - Plasminogen Activators/metabolism
PMC - PMC509128
EDAT- 1998/11/20 00:00
MHDA- 1998/11/20 00:01
PMCR- 1998/11/15
CRDT- 1998/11/20 00:00
PHST- 1998/11/20 00:00 [pubmed]
PHST- 1998/11/20 00:01 [medline]
PHST- 1998/11/20 00:00 [entrez]
PHST- 1998/11/15 00:00 [pmc-release]
AID - 10.1172/JCI3316 [doi]
PST - ppublish
SO  - J Clin Invest. 1998 Nov 15;102(10):1788-97. doi: 10.1172/JCI3316.